JP2021528173A - Therapeutic devices and methods for stimulating a patient's neurons to suppress their pathogenic synchronous activity - Google Patents

Abstract

The present invention relates to a therapeutic device for stimulating a patient's neurons to suppress pathological synchronous activity, wherein the device comprises at least three non-invasive stimulus units for generating stimuli to the patient's body and a duration of activity. Includes one control unit for selectively and intermittently operating the stimulation unit within the sequence of. The control unit is configured to variously determine the number n of stimulus units that are simultaneously activated during each activity period, throughout the sequence of activity periods.

Description

The present invention relates to therapeutic devices and methods for stimulating a patient's neurons to suppress the pathogenic synchronous activity of the neurons.

Some brain disorders, such as Parkinson's disease, are characterized by abnormally strong synchronous activity of neurons (ie, strongly synchronized neuronal launches or bursts). In addition to Parkinson's disease, this feature also includes, for example, essential tremor, ataxia, post-stroke dysfunction, epilepsy, depression, migraine, tension headache, compulsive disorder, hypersensitivity colon syndrome, chronic pain syndrome, etc. It can also apply to pelvic pain, dissociation in borderline personality disorders, and post-traumatic stress disorders.

For example, pharmacological treatment of Parkinson's disease with L-DOPA may have limited therapeutic effect and can cause very long-term side effects. Radio frequency deep brain stimulation (DBS) for Parkinson's disease is standard for patients with advanced stages of Parkinson's disease who are medically unwieldy. However, DBS requires surgery associated with great risk. For example, deep electrode implantation in a particular target area in the brain can cause bleeding. In addition, standard continuous high frequency DBS can cause side effects.

In addition, non-invasive vibration-tactile multichannel stimulation therapy is known to counteract the signs of Parkinson's disease. The drawback of this non-invasive approach lies in the essentially periodic structure of the stimuli used. In essence, stimuli may be ineffective if certain stimulus parameters, such as the repetition rate of a series of stimuli, are not properly tuned to the dominant frequency of the abnormally active neuron. Especially in non-invasive configurations, it is difficult to obtain a reliable estimate of the frequency retention of abnormal brain activity due to the limitation of long-term non-invasive electroencephalographic audiometry (EEG) recording. More importantly, some brain disorders have abnormalities at various frequencies (eg, about 4 Hz to 5 Hz associated with Parkinson's disease tremors), as opposed to 9 Hz to 35 Hz, which is associated with slowness and rigidity in Parkinson's disease. It is characterized by a healthy brain rhythm. In addition, multiple central oscillators (ie, brain rhythms) cause tremors in various limbs in patients with Parkinson's disease. In the absence of feedback signals from long-term implanted brain electrodes, it can be difficult to achieve optimal stimulation results with previously used stimulation patterns.

It was found that abnormally upregulated synaptic connections can cause abnormal synchronous activity in neurons. However, repeated and simultaneous neuronal activation can increase the strength of their mutual synaptic connections. Therefore, if the stimuli generated by the known non-invasive vibrating-tactile multichannel stimulus treatment repeatedly and simultaneously overlap with the neuronal morbid synchronous activity, this treatment can unintentionally enhance the neuronal morbid synchronous activity.

In view of the technical background, an object of the present invention is an improved non-invasive therapeutic apparatus capable of robustly and effectively suppressing the pathological synchronous activity of neurons (ie, in the patient's brain). Propose each method.

An object of the present invention is a therapeutic device having the characteristics of claim 1, a therapeutic glove having the characteristics of claim 22, a therapeutic band having the characteristics of claim 23, a therapeutic seat pad having the characteristics of claim 24, and the like. It is solved by a therapeutic shoe sole having 25 features, a therapeutic system having the features of claim 26, and a therapeutic method having the features of claim 27. Preferred embodiments are obtained from figures, specifications and dependent claims.

Therefore, in the first aspect, a therapeutic device for stimulating a patient's neurons to suppress pathological synchronous activity is proposed, the therapeutic device having at least three non-three devices for generating a stimulus to the patient's body. Includes an invasive stimulus unit. The treatment device further includes a control unit for selectively and intermittently operating the stimulation unit within the sequence of activity periods, which control unit is described above, for each period of activity, throughout the sequence of periods of activity. It is configured to variously determine the number n of stimulation units that are simultaneously activated during the period of activity of.

According to yet another aspect, therapeutic gloves, therapeutic bands, therapeutic seat pads and therapeutic soles for stimulating the patient's neurons to suppress pathological synchronization activity are proposed, each of which is a patient. The control comprises at least three non-invasive stimulus units for generating stimuli to the body and one control unit for selectively and intermittently activating the stimulus unit within a sequence of periods of activity. The units are configured to varyly determine the number n of stimulus units that are simultaneously activated during each of the active periods throughout the sequence of the active periods.

According to yet another aspect, a therapeutic system for stimulating a patient's neurons to suppress pathological synchronization activity is proposed, the therapeutic system comprising two or more therapeutic devices.

According to yet another aspect, a therapeutic method for stimulating a patient's neurons to suppress pathological synchronization activity is proposed. The method comprises providing at least three non-invasive stimulus units for generating stimuli to the patient's body and selectively and intermittently activating the stimulus units according to a sequence of periods of activity. The number n of stimulus units that are simultaneously activated during each of the active periods varies throughout the sequence, and three stimulating units are simultaneously activated during at least one of the active periods. ..

The present disclosure will be more easily understood by reference to the following detailed description when considered in connection with the accompanying drawings.

It is the schematic of the therapeutic apparatus for stimulating the neuron of a patient and suppressing the pathological synchronization activity. FIG. 5 schematically illustrates a sequence of periods of activity in which a non-invasive stimulus unit of a therapeutic device is activated to suppress the pathogenic synchronous activity of a patient's neurons. FIG. 5 is a flow diagram illustrating a procedure used by the control unit of a treatment device to generate the sequence depicted in FIG. It is the schematic of the treatment apparatus by 2nd Embodiment. FIG. 6 is a schematic view of a treatment device in the form of a treatment glove. FIG. 6 is a schematic representation of a therapeutic device in the form of a therapeutic neck and / or shoulder band. FIG. 6 is a schematic view of a therapeutic device in the form of a therapeutic laryngeal band. FIG. 6 is a schematic view of a therapeutic device in the form of a therapeutic face mask or band. It is the schematic of the treatment apparatus in the form of a therapeutic seat pad. It is the schematic of the treatment apparatus in the shape of a therapeutic belly band.

Hereinafter, the present invention will be described in more detail with reference to the accompanying drawings. In the figure, similar elements are indicated by the same reference number, and the iterative description may be omitted to avoid redundancy.

FIG. 1 schematically shows a therapeutic device 10 that stimulates a patient's neurons to suppress the pathological synchronous activity of the neurons.

The treatment device 10 can be used for the treatment of neurological or psychiatric disorders, specifically Parkinson's disease, essential tremor, ataxia and the like. For that purpose, the treatment device 10 has epilepsy, tremor as a result of multiple sclerosis, and other pathological tremors, depression, motor disorders, cerebral disorders, compulsive disorders, Tourette syndrome, post-stroke function. Disorders, spasmodic paralysis, ringing in the ears, sleep disorders, schizophrenia, irritable colon syndrome, addiction disorders, personality disorders, attention deficiency disorders, attention deficiency hyperactivity syndrome, game addiction, neuropathy, feeding disorders, burning syndrome, It can also be used to treat other neurological or psychiatric disorders such as fibromyalgia, migraine, swarm headache, general headache, nerve pain, gait, tic disorders or hypertension, as well as to treat other disorders.

The aforementioned diseases can be caused by impaired biotelecommunications of nerve cell groups connected to each other by specific pathways. This causes the neuronal population to generate continuous pathological neuronal activity and the high pathological connections (reticulated structure) that may be associated with it. In this regard, a large number of neurons form a synchronous activity potential, which means that the associated neurons fire or burst excessively and synchronously. In addition, pathological neuronal populations have vibrating neuronal activity, which means that neurons fire or burst rhythmically. In the case of neurological or psychiatric disorders, the average frequency of pathological rhythmic activity of related neuronal groups can be in the range of approximately 1 Hz to 30 Hz, but may be outside this range. In contrast, neurons in a healthy person fire or burst in a qualitatively different manner, eg, uncorrelatedly.

In other words, each of the aforementioned diseases can be characterized by at least one neuronal population in the brain or spinal cord of a patient with pathogenic synchronous neuronal activity. To suppress such pathological synchronous activity, the therapeutic device 10 is configured to stimulate the affected neural population to fire or burst the affected neural population in an uncorrelated, or asynchronous manner. ..

Specifically, the treatment device 10 is a non-invasive treatment device. This means that the therapeutic device 10 performs non-invasive treatment to achieve the intended therapeutic effect. In other words, in the operating state, the treatment device 10 is not implanted in the patient's body, i.e., not associated with interventional procedures within the patient's body.

To act on the patient's body, the treatment device 10 comprises four non-invasive stimulation units 12a-d, each of which is configured to generate a stimulus to the patient's body. In other words, the stimulation units 12a-d are configured to cause irritation to the patient's body when in contact with the patient's body surface. Therefore, the stimulation units 12a-d are intended to be immobilized on the patient. Therefore, the treatment device 10 further includes fixing means (not shown) for detachably fixing the stimulation units 12a to 12a to the patient's body. Specifically, the fixation means are provided such that the stimulation units 12a-d are fixed to various parts of the patient's body. Therefore, the stimulation units 12a to 12d are separated from each other while the treatment device 10 is fixed to the patient's body. Thus, the stimulus units 12a-d are configured to generate stimuli at various parts of the patient's body.

Although the illustrated embodiment includes four stimulation units 12a to d, a therapeutic device including three stimulation units can also achieve a satisfactory therapeutic effect. Thus, in another embodiment, the treatment device may include three or more stimulation units.

The stimuli produced by the stimulus units 12a-d generally refer to stimuli that can be perceived by the patient's body, i.e. by their respective receptors. Such stimuli can have, for example, modes of light stimulus, auditory stimulus, tactile stimulus, vibration stimulus, electrical stimulus and / or temperature stimulus. These stimuli may be perceived by receptors in the patient's eyes, ears and / or skin, depending on the mode of stimulus, from which the patient's nerves cause neuronal activity in the patient's brain or spinal cord. Guided by the system.

Therefore, in order to suppress the neural population affected by pathological synchronous activity, the stimulating units 12a-d are perceived by the receptors of the patient's body and guided to the nervous system. That is, it is configured to generate a stimulus to the patient's body that at least partially causes activity in the patient's brain. To do this, the mode and characteristics of the stimulus produced and the intended location (where the stimulus is induced within the patient's body) are each set as described in more detail below.

Each stimulus unit 12a-d can be configured to produce at least one of the aforementioned stimulus modalities. Across the plurality of stimulation units 12a-d, the stimulation units 12a-d may be configured to produce the same or different modes of stimulation.

In the embodiment shown in FIG. 1, the stimulus units 12a-d are configured to generate vibration and / or tactile stimuli, respectively. In such a configuration, the stimulation units 12a-d may include a stimulation element (such as a rod) configured to mechanically act on the patient's skin. The stimulating element can be driven by an electromechanical actuator that converts electrical energy into the motion of the stimulating element. For example, electromechanical actuators may be provided in the form of isocurrent motors, voice coils, piezoelectric converters or transformers constructed of electroactive polymers that change shape upon application of current. To provide electrical energy to electromechanical actuators, stimulation units 12a-d may include or be connected to an energy source (ie, in the form of a battery). With such a configuration, the stimulus units 12a-d can be variably driven to generate oscillating stimuli of varying or variable frequencies and amplitudes. Thus, the stimulus units 12a-d may be operated in different modes of operation, and each stimulus unit 12a-d produces different stimuli (ie, in terms of stimulus duration, frequency, amplitude, etc.).

In general, human skin has mechanoreceptor afferent units that can sense stimuli (ie, tactile or vibrational stimuli) that fall into two major categories: fast-adapting units (FA) and slow-adapting units (SA). Have. FA units respond to the attack and elimination of locomotion and step stimuli. In contrast, SA units respond to maintenance discharges. Furthermore, based on the characteristics of their receptive fields, both categories are further divided into two different types. Also called RA (fast-adapting) units, fast-adapting I (FAI) units and slow-adapting I (SAI) units constitute small but well-separated receptive fields on the surface of the skin. In contrast, the receptive field composed of fast-adapting II (FA II) units, also called PC (Pacinian corpuscle) units, and slow-adapting II (SA II) has broader and more obscure boundaries.

Typically, the distribution and density of various types of mechanical receptors will vary depending on their location on human skin. For example, with respect to the hairless skin of the human hand, the density of FAI units is relatively high within the area of the fingertips. In contrast, the area of the fingers and back of the hand has a relatively high density of FA II units.

Four different types of human skin mechanical receptors respond optimally to qualitatively different stimuli. Specifically, marginal stimulation and stretch stimulation are optimal for SA I and SA II mechanical receptors, respectively. SA I units often have a relatively irregular maintenance discharge, whereas SA II units discharge regularly but often exhibit spontaneous discharge in the absence of tactile stimuli. Oscillating vertical sinusoidal skin displacement in the range of about 30 Hz to about 60 Hz is the optimum stimulus for the FAI unit, whereas vibrating stimulus in the range of about 100 Hz to about 300 Hz is the optimum stimulus for the FA II unit. be. FAI and especially SAI units have significant edge contour sensitivity, so the response is stronger when the stimulator contactor surface is not completely included in the receptive field. Therefore, in order to enhance the FAI response, a contactor surface with a spatially non-uniform recessed cross section can be used instead of the flat, spatially uniform contactor surface of the stimulating element.

In the embodiments shown, the stimulus units 12a-d may be designed and configured to generate stimuli adapted to the response characteristics of the FA I, FA II, SA I and / or SA II units. In this configuration, the stimulus units 12a-d may be configured to generate stimuli adapted to respond to at least one of the FA I, FA II, SA I and SA II units, respectively. For example, the therapeutic device 10 may include stimulus units 12a-d configured to generate stimuli that target only one of the FA I, FA II, SA I and SA II units. In other words, these stimulus units 12a-d generate stimuli adapted to the response characteristics of one of the FA I, FA II, SA I and SA II units. Alternatively or additionally, the therapeutic device 10 may include stimulus units 12a-d configured to generate stimuli that target two or more of the FA I, FA II, SA I and SA II units. For example, such stimulus units 12a-d may be configured to generate stimuli sensed by a plurality of FA I, FA II, SA I and SA II units. Alternatively or additionally, such stimulus units 12a-d are configured to operate in different modes of operation, in which different modes of operation the various FA I, FA II, SA I and SA II units. Various stimuli adapted to the response characteristics are generated.

Specifically, when targeting FA type I receptors, stimulation units 12a-d generate vibrational stimuli with a vibrational frequency of 30Hz-60Hz (ie, 30Hz) and an intervertebral amplitude of 0.25mm. Can be configured to. For example, the stimulation units 12a-d may be intended to be anchored to the patient's fingertips. Furthermore, when targeting FA type II receptors, stimulation units 12a-d are such to generate a vibrational stimulus with a vibrational frequency of 100Hz-300Hz (ie, 250Hz) and an intervertebral amplitude of 2.0mm. Can be configured in. For example, the stimulation units 12a-d may be intended to be secured to the patient's fingers or back of the hand. Furthermore, it was found that low frequency oscillations targeting the FA type I receptor further activate the FA type II receptor and vice versa when the intervertex amplitude is sufficiently large. Therefore, the vibrational properties described above are adapted to stimulate both FA I and FA type II receptors, respectively, by increasing the intervertex amplitude to, for example, 3.0 mm. Can generate stimuli.

The treatment device 10 further includes a control unit 14 for selectively and intermittently operating the stimulation units 12a to 12d. The control unit 14 is connected to each of the stimulation units 12a to 12 via the connecting line 16, and the control signal is transmitted from the control unit 14 to the stimulation unit 12a via the connecting line 16 to operate the stimulation units 12a to 12a. It is guided by ~ d.

Specifically, the control unit 14 is configured to operate the stimulation units 12a to 12 in the sequence S of _{the continuous activity periods T A1, ..., Ai, and the letter "i" is the activity in the sequence S.} Refers to the total number of periods. FIG. 2 shows a sequence S of continuous activity periods T _{A1, ..., Ai} , and according to this sequence S, the stimulation units 12a to 12a of the treatment device 10 suppress the pathological synchronous activity of the patient's neurons. Is activated. The sequence S is generated by the control unit 14 and forms a control sequence or control pattern showing the activity of the stimulation units 12a to 12d over time. Therefore, the sequence S indicates the time period during which the stimulation units 12a to 12d of the treatment device 10 are selectively and intermittently operated. The sequence S of activity periods _{TA1, ..., Ai} may have a duration corresponding to the duration of the treatment (eg, daily treatment) performed by the treatment device 10. For example, sequence S can have a duration of 120 minutes.

Sequence S includes time-shifted, non-overlapping activity periods T _{A1, ..., Ai} of number i. In this context, the term "period of activity" refers to a period of time within Sequence S, the period during which at least one of the stimulation units 12a-d is activated to generate a stimulus to the patient's body. Therefore, the duration of the activity periods _{TA1, ..., Ai} corresponds to the length of the single stimulus produced by the stimulus units 12a-d. For example, the activity periods _{TA1, ..., Ai} can have a duration of 25 ms to 3 seconds (ie, about 125 ms). In alternative embodiments, the periods of activity within the sequence can at least partially overlap.

As depicted in FIG. 2, a rest period T _{R1, ..., Ri} is scheduled _{between the continuous activity periods T A1, ..., Ai.} The term "rest period" refers to a period within sequence S in which none of the stimulation units 12a-d are activated. Therefore, during the rest period _{TR1, ..., Ri} , the patient's body does not receive the stimuli generated by the stimulus units 12a-d of the treatment device 10.

In FIG. 2, the activity of each of the stimulation units 12a to 12d is shown by a dashed line range positioned within _{the activity periods TA1, ..., Ai.} During the active periods _{TA1, ..., Ai} , the control unit 14 may exclusively activate the single stimulus unit 12 as depicted by the _{active periods TA1} , _TA5 and _{TAi in FIG.} Alternatively, as depicted by the activity period T _A2, T _A3 and T _A4 in FIG. 2, the control unit 14, activity period T _{A1, ...,} a plurality in _Ai (e.g., 2 or 3) The stimulation units 12a to 12d can be operated at the same time. In the shunt of the present disclosure, the number of stimulus units 12a-d that are simultaneously activated during _{each activity period TA1, ..., Ai is shown as "n 1, ..., i} ", where n is It is an integer greater than 1. If n is equal to 1, this means that the single stimulus units 12a-d are individually activated during _{each of the active periods TA1, ..., Ai.} In contrast, when n exceeds 1, this means that two or more (ie, n) stimulation units 12a-d are simultaneously activated _{during each period of activity TA1, ..., Ai.} Means. In the sequence S depicted in FIG. 2, n ₁ , n ₅ and n _i are 1, n ₂ and n ₃ are 2, and n ₄ is 3.

More specifically, the control unit 14, activity period T _{A1, ...,} throughout the sequence S of _Ai, activity period T _{A1, ...,} each _Ai, stimulation unit is activated each activity period It is configured to variously determine the numbers n _{1, ..., I of 12a to d.} In this context, the term "various" means that _{the values of the numbers n 1, ..., i} vary throughout the sequence S, i.e., aperiodically.

Again, with this configuration, the control unit 14 can determine a value of 1 for the _{number n 1, ..., i} , i.e., a single stimulus unit during _{each activity period TA 1, ..., Ai.} Only 12a-d are activated. In contrast, if the control unit 14 determines a value greater than _{1 in the number n 1, ..., i} , this means multiple stimuli during the _{period of activity TA 1, ..., Ai.} It means that the units 12a to 12d are operated at the same time.

Specifically, in order to increase the diversity of neuronal activation induced by the stimulation, the control unit 14, activity period T _{A1, ...,} with respect to at least one of _Ai, the activity period T _A4 in FIG. 2 As depicted, it is configured to determine at least three stimulus units 12a-d that are activated simultaneously. In other words, the control unit 14 is configured to determine a value of 3 or more for at least one of _{n 1, ..., I.}

In the embodiments shown, the control unit 14 can determine values from 1 to a preset maximum number of simultaneously activated stimulus units for the _{numbers n 1, ..., i.} Therefore, the numbers n _{1, ..., I} are integers from 1 to the maximum number of stimulus units that are simultaneously activated. The maximum number may correspond to the total number of stimulation units 12a-d included in the treatment device 10. It has been found that when the treatment device 10 includes more than three stimulus units, it is less preferable to operate all the stimulus units at the same time. Therefore, the maximum number of simultaneously activated stimulation units can correspond to a number smaller (ie, one less) than the total number of stimulation units 12a-d included in the treatment device 10.

Sequence S whole several n _{1, ...,} in order to variously determine _i, the control unit 14, activity period T _{A1, ...,} for each _Ai, the number n _1,. Stimulation unit 12a~d _{.., i} is configured to be determined stochastically and / or deterministically and / or by a combination of probability theory and determinism. For example, for that purpose, the control unit 14 may use an exponential distribution process and / or a Markov process and / or any other suitable stochastic or deterministic or combination of probabilistic and deterministic processes. In this way, regularity or periodicity within Sequence S can be avoided, thereby robustly and effectively suppressing the pathological synchronous activity of the patient's neurons.

In yet another evolution, the process of determining _{the number n 1, ..., i of the stimulus units is performed so that the values of the numbers n 1, ..., i} are provided with equal or different probabilities. sell. In this way, the frequency of occurrence of individual values of the _{numbers n 1, ..., I can be set over the entire sequence S.} For example, in the sequence shown _{, the value 1 of the numbers n 1, ..., i} is provided with a 50% probability, the value 2 is provided with a 33% probability, and the value 3 is provided with a 16% probability. Can be provided. As a result, in the sequence S having an activity period of i = 6 _{, the value 1 of n 1, ..., i} is determined for the three activity periods, and n _{1, ... is} determined value 2 of _i is, n ₁ is the one activity _{period, ...,} the value of _i 3 can be determined.

Further, the control unit 14 has a _{predetermined number n 1, ..., I} from a set of stimulation units including at least three stimulation units 12a to d over the entire sequence S _{of the activity period T A1, ..., Ai.} The various stimulus units of the above are configured to be variously selected, and the selected stimulus units 12a to 12a are operated individually or simultaneously during the _{respective activity periods TA1, ..., Ai.} In this context, the term "various" means that the selected stimulus unit changes differently (ie, aperiodically) throughout the sequence S.

For example, when the control unit 14 is determined to have a specific activity period T _{A1, ..., Ai in which the respective numbers n 1, ..., I} are 1, the control unit 14 has each activity period T. A single stimulus unit is selected from a set of four stimulus units 12a to d that are individually actuated during _{A1, ..., Ai.} In contrast, if the control unit 14 is determined for a particular activity period T _{A1, ..., Ai} where the respective numbers n _{1, ..., i} are 2, the control unit 14 will be, respectively. Two different stimulus units are selected from a set of four stimulus units 12a to d that are simultaneously activated during the activity period _{TA1, ..., Ai.}

To further increase the diversity of stimulus-induced neuronal activity, the control unit 14 is further subjected to at least the first and second periods of activity (eg, _TA1 and _TA5 ), as depicted in FIG. , The numbers n ₁ , n ₅ are configured to be set to a value of 1. Next, the control unit 14 selects the first stimulation unit 12a for the first _{activity period T A1} which is operated individually during _{the respective activity periods T A1} and T _{A5 , and sets the second activity period T A5} . The second stimulus unit 12c is configured to be selected. In other words, the control unit 14 selects a single first stimulus unit that is individually actuated during the first activity period and a single second stimulus unit that is individually actuated during the second activity period. Is configured to select.

Further, the control unit 14 is configured to set the number n ₃ to a value of 2 during the third activity period (eg, _TA3). Next, the control unit 14, with respect to the third activity period T _A3, 2 pieces of stimulation unit 12a to be simultaneously operated during a third period of activity T _A3, configured to select 12c. In other words, the control unit 14 is configured to select at least two stimulus units that are simultaneously activated during the third active period.

In order to variously select the stimulation units 12a to d to be operated during the sequence S, the control unit 14 sets a predetermined number n from one set of the stimulation units 12a to d in _{each activity period TA1, ..., Ai. The stimulus units 1, ..., i} can be configured to be selected stochastically and / or deterministically and / or in a combination of probability theory and determinism. For example, for that purpose, the control unit 14 may use an exponential distribution process and / or a Markov process and / or any other suitable stochastic or deterministic or combination of probabilistic and deterministic processes. Thus, regularity or periodicity within Sequence S can be avoided, resulting in a robust and effective suppression of the pathological synchronous activity of the patient's neurons.

In yet another evolution, the stimulation units 12a-d may be provided with equal or different probabilities selected by the control unit 14. Therefore, the control unit can select the stimulation units 12a to 12d with a predetermined probability of the individual stimulation units 12a to d. In this way, the frequency of occurrence of the individual stimulus units 12a-d to be activated can be set throughout the sequence S. For example, the individual stimulus units 12a-d may be provided with a higher relative probability so that they are activated more frequently during the sequence S.

As an addition or alternative, the control unit 14 is a single stimulus unit 12a-d and / or an activity within the sequence S that is individually or exclusively actuated during the _{period of activity TA1, ..., Ai within the sequence S.} period T _{A1, ...,} for the combination of the stimulation unit 12a~d to be simultaneously activated during _Ai, each activity period by a predetermined probability or predetermined frequency T _{A1, ...,} stimulation of _Ai unit 12a~ It can be configured to select d. For example, for a combination of two stimulation units 12a-d, the probability or frequency of occurrence may be set to 0 to avoid having these two stimulation units 12a-d actuated simultaneously during sequence S. .. In other words, a given probability or frequency of occurrence is that a single stimulus unit 12a-d is actuated individually or exclusively during sequence S and / or a particular combination of stimulus units 12a-d is actuated simultaneously. Can be set to prevent. In yet another example, the probability or frequency of occurrence of a particular single stimulus unit 12a-d being activated individually and / or a particular combination of stimulus units 12a-d being simultaneously actuated during sequence S. The stimulus unit can be set relatively high for more frequent operation. Further, the predetermined probability or frequency of occurrence may change during the sequence S.

As mentioned above, the stimulus units 12a-d may be operated in various modes of operation, and each stimulus unit 12a-d may be operated in various stimuli (ie, in terms of stimulus duration, frequency, amplitude, etc.). ) Is generated. Therefore, the control unit 14 is configured to variously select one operation mode from a predetermined set of operation modes of the respective stimulation units 12a to d for each of the selected stimulation units 12a to d.

In the embodiments shown, as depicted in FIG. 2, the stimulation units 12a-d are in a first mode of operation designated as "O1" and a second mode of operation designated as "O2", respectively. The modes of operation of the respective stimulus units 12a-d may be activated by the stimulus units 12a-d, eg, in terms of stimulus duration, stimulus intensity, eg tremor amplitude, stimulus frequency and / or stimulus aging. The characteristics of the stimuli generated are different. In FIG. 2, different operating modes O1 and O2 are shown by shading with different operating ranges.

Specifically, in order to select various operation modes, the control unit 14 selects one operation mode from a predetermined set of operation modes of the respective stimulation units 12a to 12 for each of the selected stimulation units 12a to d. It is configured to choose between stochastic and / or deterministic and / or a combination of probabilistic and deterministic. To do so, the control unit 14 may use an exponential distribution process and / or a Markov process and / or any other suitable stochastic or deterministic or stochastic and deterministic combined process.

As described above and depicted in FIG. 2, a rest period T _{R1, ..., Ri} is scheduled _{between consecutive activity periods T A1, ..., Ai.} These rest periods _{TR1, ..., Ri} are generated or defined by the control unit 14. Specifically, the control unit 14 is configured to variously determine the duration _{of each rest period TR1, ..., Ri in the sequence S.} In this context, the term "variously" means that _{the predetermined duration of the rest periods TR1, ..., Ri} varies (ie, aperiodically) throughout the sequence S. The control unit 14 sets the _{duration to 0 seconds for at least one rest period TR1, ..., RI} , resulting in two consecutively scheduled activity periods T _{A1, ..., Ai.} Can be configured to continue in sequence.

In order to variously determine the rest period _{TR1, ..., Ri} , the control unit 14 determines the duration of the rest period _{TR1, ..., Ri} probabilistically and / or deterministically, and / or. It is configured to be determined by a combination of stochastic theory and deterministic theory. For example, for that purpose, the control unit 14 may use an exponential distribution process and / or a Markov process and / or any other suitable stochastic or deterministic or stochastic and deterministic combined process. Thus, regularity or periodicity within Sequence S that can adversely interfere with the periodicity inherent in pathological synchronization and oscillatory neuronal activity can be avoided.

To facilitate handling, in the following, the sum of the activity period T _Rx and subsequent rest period T _Rx is referred to as the operating cycle T _Cx. It has been found that slight periodicity or repetition within a set of working cycles T _{C1, ..., Ci} in the sequence typically does not impair the therapeutic effect of the proposed therapeutic device 10. For example, even if a set of determined working cycles T _{C1, ..., Ci} comprises 10% of the duration of the same rest period, the proposed treatment device 10 still provides the intended therapeutic effect. Can be done. However, the control unit 14 has _{a rest period TR1, ... such that a set of predetermined operating cycles T C1, ..., Ci comprises} 10%, 5% or less than 1% of the same duration. _{, Ri} can be configured to determine the duration.

Alternatively, the control unit 14 in sequence S has a dormant period _{TR1, ..., Ri} or an actuation cycle T _{C1, ..., Ci} having an equal duration _. It can be configured to specify or generate _Ri.

As mentioned above, some brain disorders are associated with abnormal neuronal vibrational activity characteristic of certain frequency bands. For example, deep recordings in the basal ganglia of patients with Parkinson's disease revealed vibration-related theta-band (4 Hz to 7 Hz) activity and bradykinesia-related beta-band (9 Hz to 35 Hz) activity. Specifically, abnormal neuronal oscillations can be found in various frequency bands.

Therefore, the control unit 14 has a rest period TR1, such that the average frequency of the activity sequence S does not exceed the upper band edge of the lowest frequency band associated with brain disease (eg, 7 Hz in Parkinson's patients with tremor) _{. ...,} can be configured to determine Ri. The average frequency corresponds to or can be calculated by the reciprocal of the sum of the duration of the average activity period and the duration of the average rest period in the sequence S. Alternatively, the control unit 14 allows the average frequency of the activity sequence S to be within 5% of the lowest dominant frequency associated with brain disease, or up to 2 or 5 times lower than the dominant frequency associated with brain disease. , The rest period _{TR1, ..., Ri} can be configured to determine.

FIG. 3 shows a flow diagram showing the procedure used by the control unit 14 to generate the sequence S. The procedure can be performed by the control unit 14 before activating the stimulation units 12a-d according to the generated sequence S. Alternatively, this procedure can be performed continuously during sequence S, i.e. during operation of stimulation units 12a-d.

In the following, the steps of the procedure will be described in more detail with reference to FIG. Sequence S includes various activity periods T _{A1, ..., Ai} of number i, as depicted in FIG. In the procedure shown, steps S2 to S10 are repeated and continuously performed _{during each activity period TA1, ..., Ai.}

In step S1, the value of the control variable x is set to 1. Thus, in step S2~S7 procedure, first, the first activity period T _A1 of the sequence S is generated. Specifically, in step S2, the control unit 14, various numbers n ₁ stimulation unit 12a~d actuated during activity period T _A1, i.e. probabilistic and / or deterministic, and / or It is decided by a combination of probability theory and determinism. Next, in step S4 to S7, the control unit 14, the four stimulation unit stimulation unit a predetermined number n ₁ from 12a~d treatment apparatus 10 successively selects, these steps activity period T _{A1 , ..., Ai} is performed so that each of the plurality of stimulation units 12a to 12a can be selected only once. Specifically, for each of the selected stimulation units 12a to d, the control unit 14 sets various operation modes from a predetermined set of operation modes, that is, probabilities, with respect to the stimulation units 12a to d selected in step S5. Select theoretically and / or deterministic and / or a combination of probability theory and determinism.

Then, in step S8, the control unit 14 determines the duration of the rest period _TR1 variously, i.e. stochastically and / or deterministically, and / or a combination of probabilistic and deterministic. Next, in step S9, the control variable x is incremented by 1, and in steps S2 to S9 described above, the control variable x exceeds the total number i of the _{various activity periods TA1, ..., Ai generated in the sequence S.} Is repeated until.

FIG. 4 shows another embodiment of the treatment device 10. Compared to the embodiment depicted in FIG. 1, the medical device 10 of FIG. 4 includes means for closed-loop control of the stimuli generated by the stimulus units 12a-d. Thus, the therapeutic device 10 further includes a sensor unit 18 for measuring or assessing the stimulating effect and / or neuronal activity, i.e., the patient's brain or spinal cord and / or muscle activity. Therefore, the treatment device 10 comprises yet another fixing means for coupling the sensor unit 18 to the patient's body. The sensor unit 18 is connected to the control unit 14 via a connection by 20, which leads the measured or accessed information or data to the control unit 14. Alternatively, the sensor 18 may be wirelessly connected to the control unit 14.

In this configuration, the control unit 14 is configured to generate or adapt a sequence S of _{continuous activity periods TA1, ..., Ai based on the information acquired by the sensor unit 18. Specifically, the control unit 14 determines the number n 1, ..., I based} on the information acquired by the sensor 18, and determines the predetermined number n _{1 , ..., I for each activity period TA 1, ..., Ai. ..,} select different stimulus units 12a-d of i, select operation mode for each selected stimulus unit 12a-d, and / or determine the duration of _{each rest period TR1, ..., Ri} do.

The sensor unit 18 may include at least one non-invasive sensor. For example, this includes electroencephalography (EEG) recording (evaluation of brain activity), electromagnetic encephalography (MEG) recording (evaluation of brain activity), electromyography (EMG) recording (muscle activity (eg, tremor)). It may include a sensor to obtain the evaluation) of the war). Further, the sensor unit may include a sensor for registering motion parameters such as an accelerometer (measuring tremor or momentum).

Alternatively or additionally, the sensor unit 18 may include at least one invasive sensor. For example, such an invasive sensor is an electrode (eg, on) configured to be implanted in the patient's brain to provide a signal generated by an active neuron (specifically, a local electric field potential (LFP)). Can be provided in the form of cortex, epidural, intracortical or depth electrodes). A less invasive alternative is a subcutaneous electrode (ie, an electrode implanted under the skin of the head).

More specifically, in one embodiment, the control unit 14 uses the information or data acquired by the sensor unit 18 to generate stimulus characteristics (eg, stimulus duration, stimulus intensity, etc.) by the stimulus units 12a-d. It can be configured to adapt to the stimulus frequency and / or the stimulus over time). For example, if the sensor unit 18 detects or measures high levels of disease-related spectral power in EEG, MEG, EMG or LFP recordings, the control unit 14 will be the single stimulus generated by the stimulus units 12a-d. It may be configured to increase the stimulation intensity respectively by increasing the amplitude and / or duration.

In yet another evolution, the control unit 14 may be configured to repeatedly adapt to the stimulus features generated by the stimulus units 12a-d, with the information or data acquired by the sensor unit 18. Specifically, the control unit 14 may be configured to analyze the acquired data of the sensor unit 18 and selectively adapt to the characteristics of the stimuli generated by the stimulus units 12a-d. For example, the control unit 14 may perform spectroscopic analysis based on the EEG, MEG, EMG and / or LFP records acquired by the sensor unit 18. The control unit 14 is then triggered by changes in brain activity, specifically by stimulating the patient's body with stimulation units 12a-d, over a time period of one or more treatments performed by the treatment device 10. It may be configured to register changes in spectral power in other disease-related frequency bands (eg, theta and / or beta band in Parkinson's disease). The stimulus characteristics generated by the stimulus units 12a-d are then changed stepwise or iteratively to change the spectral power and track the change by the sensor unit 18. Parameters or features such as the vibration width or amplitude of the electrical pulse that causes the unilateral or bidirectional stimulus, the length of a single vibration or electrical stimulus, the number of stimulators, the position of the stimulus units 12a-d in the patient's body. At least one of can be changed. In this way, the control unit 14 can automatically identify and adapt the associated features or parameters of the stimulus that most significantly reduce the disease-related spectral power.

Further, the information or data acquired by the sensor unit 18 is adapted by the control unit 14 to the average frequency of the activity sequence, that is, the rest periods _{TR1, ..., Ri} in the sequence S are changed, respectively. Can be used by. For example, the control unit 14 can perform spectroscopic analysis based on the EEG, MEG, EMG and / or LFP records acquired by the sensor unit 18 to determine the dominant vibration frequency component. Based on this, the control unit 14 adapts the average frequency of the activity sequence S so that the average frequency is in the range of ± 5% of the lower limit of the lowest dominant frequency of the feedback signal, or the lowest dominant frequency of the feedback signal. It can be configured to be at the lower edge or up to 2 times and even up to 5 times the lowest dominant frequency of the feedback signal.

As an addition or alternative, the control unit 14 may be configured to generate a warning signal to the patient based on the data or information acquired by the sensor unit 18, which indicates, for example, to increase the daily treatment time. .. Therefore, the treatment device 10 may include means for outputting a warning signal (eg, a display device or a transmission unit). Specifically, the transmitting unit may be configured to output the warning signal to the patient's mobile device (such as a mobile phone) that can display the warning signal to the patient.

FIG. 5 schematically shows a therapeutic device in the form of a therapeutic glove 22 that can be wirelessly coupled to a sensor unit 24 to stimulate a patient's neurons to suppress pathological synchronization activity. The therapeutic glove 22 may be fixed to the patient's right hand 26 and the sensor unit 24 may be fixed to the patient's head 25. In this configuration, the sensor unit 24 is not essential.

The therapeutic glove 22 constitutes the therapeutic device 10 as described above. Therefore, the technical features described above with respect to the therapeutic device 10 may also be relevant and applicable to the therapeutic glove 22.

The therapeutic glove 22 comprises five first stimulus units 12a-e fixed to different fingers (ie, fingertips) of the patient's hand 26 and at least one second stimulus fixed to the back of the patient's hand. Includes unit 12f. Stimulation units 12a-f may include qualitatively different mechanical stimulators. For example, the first stimulation units 12a-e may include a piezovibrator and the second stimulation unit 12f may include a linear motor or voice coil.

Further, the therapeutic glove 22 includes a control unit 14 for selectively and intermittently operating the stimulation units 12a to 12 within the sequence of activity periods, the control unit 14 performing the activity period throughout the sequence of activity periods. Each is configured to variously determine the number n of stimulus units that are simultaneously activated during each activity period. The control unit 14 ensures that two first stimulus units 12a-e and / or all first stimulus units 12a-e fixed to two adjacent fingers are simultaneously activated during the sequence. It can be configured to prevent.

The therapeutic glove 22 further includes a wireless communication unit 28 that is connected to the control unit 14 and configured to allow communication between the control unit 14 and the sensor unit 24. Rechargeable batteries (not shown) for supplying electrical energy to each of the stimulation units 12a to f, the control unit 14, and the wireless communication unit 28 are provided. Further, the stimulation units 12a to f, the control unit 14, the wireless communication unit 28 and the rechargeable battery are embedded in the therapeutic glove 22 by removable velcro fixing means.

The sensor unit 24 is configured to measure the stimulating effect and neuronal activity of neurons in the patient's head 25. In order to transmit the information or data thus acquired to the control unit 14, the sensor unit 24 includes yet another communication unit 30 for wireless communication with the communication unit 28 of the therapeutic glove 22.

More specifically, to measure stimulus effects and neuronal activity, the sensor unit 24 has two non-invasive EEG electrodes 34 connected to the controller 36 of the sensor unit 24. In an alternative embodiment, the sensor unit 24 is an invasive electrode (not shown) (eg, upper cortex) configured to be implanted or implanted in the patient's head 25 and connected to the controller 36 as an alternative or in addition. Electrodes) can be included.

The controller 36 amplifies and analyzes the signal provided by the electrode 34, and wirelessly transmits the information thus acquired to the control unit 14 of the therapeutic glove 22 via the communication units 28 and 30. In an alternative embodiment, the control unit 14 of the therapeutic glove 22 may be connected to the controller 36 of the sensor unit 36 by a connecting line.

In yet other developments, additional therapeutic gloves for the patient's left hand may be provided. Yet another therapeutic glove is a patient with five first stimulating units fixed to different fingers (ie, fingertips) of the patient's left hand, similar to the configuration of the therapeutic glove 22 for the patient's right hand. It may be equipped with at least one second stimulation unit fixed to the back of the left hand. Further, it may include a stimulus unit and a control unit connected to the wireless communication unit, respectively, in order to wirelessly connect the control unit of the left therapeutic glove to the control unit 14 of the right therapeutic glove 22. Specifically, the control unit 14 of the right therapeutic glove 22 can function as a central control device that generates control signals to activate both the right and left therapeutic glove stimulation units according to a sequence of activity periods. .. Therefore, the control unit of the left therapeutic glove may be configured to receive a control signal from the control unit 14 of the right therapeutic glove 22, and each stimulation unit is operated according to the control signal. In this configuration, the therapeutic gloves for the left and right hands, together with the sensor unit, constitute a therapeutic system for stimulating the patient's neurons to suppress their pathological synchronization activity. The treatment system can further and / or include other treatment devices, the operation of which is controlled by a central control device associated with the control unit of one of the treatment devices, or with the treatment device. Can be associated with a separately provided central controller (eg, a personal computer).

FIG. 6 schematically shows a therapeutic device in the form of a therapeutic neck and / or shoulder band 38 for stimulating a patient's neurons to suppress pathological synchronization activity that can be wirelessly coupled to the sensor unit 24. The therapeutic neck and / or shoulder band 38 may be fixed to the patient's neck and / or shoulder, and the sensor unit 24 may be fixed to the patient's head 25. In this configuration, the sensor unit 24 is not essential.

The therapeutic neck and / or shoulder band 38 constitutes the therapeutic device 10 as described above. Therefore, the technical features described above in connection with the therapeutic device 10 and / or the therapeutic glove 22 may also be applied in connection with the therapeutic neck and / or shoulder band 38.

The medical neck and / or shoulder band 38 comprises a plurality of first stimulation units 12a-c fixed to the patient's neck and / or a plurality of second stimulation units 12d-i fixed to the patient's shoulder. The first and second stimulus units can be configured to generate a vibrating stimulus having a vibration frequency of 10 Hz to 300 Hz (ie, 70 Hz to 120 Hz) and an intervertebral amplitude of up to 0.8 mm.

FIG. 7 schematically shows a therapeutic device in the form of a therapeutic laryngeal band 40 that can be wirelessly connected to the sensor unit 24 to stimulate a patient's neurons to suppress pathological synchronization activity. The therapeutic laryngeal band 40 may be secured to the patient's neck by a neck band or neck cuff, and the sensor unit 24 may be secured to the patient's head 25. In this configuration, the sensor unit 24 is not essential. The therapeutic laryngeal band 40 constitutes the therapeutic device 10 as described above. Therefore, the technical features described above may also be relevant and applicable to the therapeutic laryngeal band 40. The therapeutic laryngeal band 40 includes a plurality of stimulation units within the area of the patient's larynx.

FIG. 8 schematically shows a therapeutic device in the form of a therapeutic face mask or band 42 for stimulating a patient's neurons to suppress pathological synchronization activity that can be wirelessly coupled to the sensor unit 24. The therapeutic face mask or band 42 may be secured to the patient's face by the band or mask and the sensor unit 24 may be secured to the patient's head 25. In this configuration, the sensor unit 24 is not essential. As described above, the therapeutic face mask or band 42 constitutes the therapeutic device 10. Therefore, the technical features described above may also be relevant and applicable to therapeutic face masks or bands 42. The therapeutic face mask or band 42 includes a plurality of stimulation units 12 located on the skin of the patient's face.

FIG. 9 schematically shows a therapeutic device in the form of a therapeutic seat pad 44 for stimulating a patient's neurons to suppress pathological synchronization activity that can be wirelessly coupled to the sensor unit 24. The therapeutic seat pad 44 is provided and configured so that the patient can sit on it. The sensor unit 24 may be fixed to the patient's head 25. In this configuration, the sensor unit 24 is not essential. As described above, the therapeutic seat pad 44 constitutes the therapeutic device 10. Therefore, the technical features described above may also be relevant and applicable to the therapeutic seat pad 44. The therapeutic seat pad 44 includes a plurality of stimulation units 12 located within the therapeutic seat pad 44.

FIG. 10 schematically shows a therapeutic device in the form of a therapeutic belly band 46 that can be wirelessly coupled to a sensor unit 24 to stimulate a patient's neurons to suppress pathological synchronization activity. The therapeutic abdominal wrap 46 may be anchored to the body within the area of the patient's abdomen and the sensor unit 24 may be anchored to the patient's head 25. In this configuration, the sensor unit 24 is not essential. As described above, the therapeutic belly band 46 constitutes the therapeutic device 10. Therefore, the technical features described above can also be applied in connection with this therapeutic belly band 46. The therapeutic abdominal wrap 46 includes a plurality of stimulation units 12a-h located within the area of the patient's abdomen.

It will be apparent to those skilled in the art that these embodiments and items merely represent examples of multiple possibilities. Therefore, the embodiments presented herein should not be understood to constitute such features and configuration restrictions. Any possible combination and configuration of the described features can be selected according to the scope of the invention.

This applies in detail to the following optional features that can be combined with some or all of the aforementioned embodiments, items and / or features in any technically feasible combination.

A therapeutic device for stimulating the patient's neurons to suppress pathological synchronization activity may be suggested. The therapeutic device may include at least three non-invasive stimulus units to generate stimuli to the patient's body. The treatment device further includes a control unit for selectively and intermittently operating the stimulus unit within the sequence of activity periods, the control unit for each period of activity, for each period of activity, throughout the sequence of periods of activity. It can be configured to variously determine the number n of stimulation units that are simultaneously activated.

As mentioned above, the abnormally strong synchronous activity of neurons that causes some brain diseases (ie, Parkinson's disease) can be triggered by abnormally upregulated synaptic connections. Down-regulation of synaptic weight is particularly preferred to permanently counteract abnormal neuronal synchronization processes over a long period of time.

It has been found that effective downregulation of abnormal synaptic weight can be achieved by activation of neural populations by mutually time-shifted activation of neural populations of various configurations (ie, in terms of position and quantity). Therefore, by providing control units that variously determine the number n of stimulus units that are simultaneously activated within a sequence of continuous activity periods, the proposed device provides a variety of neuronal activations that are pulled by the stimulus. Definitely improve and enhance. As a result, the neural population stimulated by the stimulation unit differs between periods of activity in one and another periods of activity, both in terms of location and quantity. Thereby, this device makes it possible to effectively suppress the pathological synchronization activity of neurons, that is, by desynchronizing the pathological synchronization activity of neurons.

To that end, in known non-invasive multichannel stimulation therapy devices, a plurality of different stimuli are generated according to a predetermined periodic stimulation pattern that is frequently repeated (ie, in a continuous loop) during treatment. Furthermore, such periodic stimulation patterns have been found to activate neurons caused by repetitive and overlapping production stimuli consistent with pathological synchronous activity during treatment. In contrast, the proposed therapeutic device provides time-shifted activation of neural populations of varying configurations. In this way, it is possible to avoid periodic stimulation of specific neural populations. Therefore, the proposed treatment device is more robust to detuning between the stimulus delivery rate and the predominant frequency of pathological neuronal vibrations compared to known non-invasive multichannel stimulation treatment devices. This is especially preferred when the treatment device is operated non-invasively, i.e., when there is no feedback from an implantable invasive sensor such as a superior cortical electrode.

In yet another evolution, the control unit may be configured to determine at least three stimulus units that are activated simultaneously for at least one of the active periods of the sequence. In other words, the control unit sets the value of n to 3 for at least one of the active periods of the sequence. Alternatively or additionally, the control unit determines or sets the value of n to 1 for at least one of the active periods of the sequence so that a single stimulus unit is activated individually or exclusively during each active period. Can be configured to Alternatively or additionally, the control unit is configured to determine or set the value of n to 2 for at least one of the active periods of the sequence so that two stimulus units are activated simultaneously during each active period. Can be done. In this way, a high degree of diversity of activity sequences can be assured, resulting in uncorrelated firing or bursting of patient neurons, thereby abnormally upregulated synaptic weight within the patient's target neural population. Can be significantly and surely reduced.

Stimulation units can be configured to generate stimuli in different parts of the patient's body. In this way, the therapeutic device can stimulate a larger neural population, thereby increasing the spatial diversity of the stimulated neurons. Specifically, the stimulus unit can be configured to generate stimuli on the patient's body surface. Alternatively or additionally, the stimulus unit may be configured to generate tactile and / or vibrational and / or electrical stimuli.

The control unit may be configured to determine a value of number n, an integer between 1 and the total number of stimulation units included in the treatment device. Alternatively, when the device contains more than 3 stimulus units, the value of number n may be an integer between 1 and u-1.

In order to determine the number n in various ways, the control unit determines the number n of stimulus units that are simultaneously activated during each activity period, probabilistically and / or deterministically, and / or probabilistic. It can be configured to be determined by a combination of determinism and determinism.

Further, the control unit is configured to variously select a predetermined number of different stimulation units from at least three stimulation units of the device throughout the sequence of activity periods. For example, the control unit may select a single first stimulus unit that is individually actuated during the first activity period and a single second stimulus unit that is individually actuated during the second activity period. Can be configured in. In addition, the control unit may be configured to select at least two stimulus units that are simultaneously activated during the third period of activity. Specifically, the control unit probabilistically and / or deterministically, and / or probabilistically and deterministically, probabilistically and / or deterministically selects a predetermined number of n stimulation units from at least three stimulation units of the treatment device for each period of activity. Can be configured to select in combination of.

Alternatively or additionally, the control unit combines the stimulus units for each period of activity with a single stimulus unit that is activated individually during the period of activity within the sequence and / or a combination of stimulus units that are simultaneously activated during the period of activity within the sequence. Can be configured to be selected according to a given probability or a given frequency of occurrence. For example, the probability or predetermined frequency of occurrence can be set to prevent single stimulus units from being activated individually within the sequence and / or from a particular combination of stimulus units being activated simultaneously within the sequence.

Alternatively or additionally, the control unit may be configured to variously select one motion mode from a predetermined set of motion modes for each stimulus unit for each of the selected stimulus units. The mode of operation of each stimulus unit may differ in the characteristics of the stimulus produced by the stimulus unit in terms of stimulus duration, stimulus intensity, stimulus frequency and / or stimulus time lapse.

For example, the stimulus generated can be specified based on an amplitude curve that points to changes in stimulus intensity over time. In this context, stimuli can be generated in various waveforms, for example when provided in the form of mechanical stimuli or vibrations. In particular, the control unit may be configured to variously set different stimulus waveforms during a series of activity periods and / or during each activity period. For example, to do so, the control unit may use the exponential distribution process and / or the Markov process and / or any other suitable stochastic or deterministic or combination of probabilistic and deterministic processes. Specifically, the stimulus can be generated to be provided in the form of a sinusoidal or trapezoidal wave.

It was found that different waveforms can activate proprioceptive receptors differently because different waveforms can have different power spectra. With respect to the entity, the spectrum of the trapezoidal waveform may contain higher frequency components. Therefore, in the case of the known tuning characteristics of the above-mentioned RA (fast adaptation) unit and the above-mentioned PC (Pacinian corpuscle) unit, the vibration of 30 Hz having a sine wave of sufficiently small amplitude is the fast-adaptation type I (FAI). It can activate the receptors of the RA unit, also called the unit, i.e. dominate. In addition, a 30 Hz vibration with a trapezoidal waveform that has substantially the same or the same amplitude as the sine wave can activate the receptor for the PA unit, also referred to as the fast-adapted II (FA II) unit.

Thus, in order to change the range and composition of neuronal subpopulations stimulated by different vibrational stimuli sent to the same part of the body, eg, the same fingertips, the stimulus waveform (specifically within the sequence) is, for example, a stimulus. It can be changed by another stimulus, and more specifically by deterministic or stochastic or a combination of determinism and probability theory.

In yet another evolution, the control unit may be configured to specify a period of rest between consecutive periods of activity. Therefore, the control unit may be configured to variously determine the duration of each rest period throughout the sequence. In this way, a higher variety of activity sequences can be assured, resulting in uncorrelated firing or bursting of the patient's neurons, thereby abnormally upregulated synaptic weight within the patient's neural population. Allows for remarkable and robust reduction of. Specifically, the control unit is configured to determine the respective duration of the rest period stochastically and / or deterministically and / or in combination with probability theory and determinism.

The therapeutic device could further include a sensor unit for measuring the effect of the stimulus on the neuron, the control unit measuring the stimulus generated by the stimulus unit and / or the sequence of activity periods by the sensor unit. It can be configured to be more adapted to the information.

In addition, therapeutic gloves that are fixed in the patient's hand and stimulate the patient's neurons to suppress pathological synchronization activity may be proposed. As mentioned above, the therapeutic glove may constitute or include a therapeutic device. Therefore, the technical features described for the therapeutic device may also be relevant and applicable to this therapeutic glove.

In addition, therapeutic bands that are immobilized on the patient's body and stimulate the patient's neurons to suppress pathological synchronization activity can be proposed. The therapeutic band may constitute or include a therapeutic device as described above. Therefore, the technical features described with respect to the therapeutic device may also be relevant and applicable to this therapeutic band. Specifically, the therapeutic band may be a therapeutic neck and / or shoulder band, a therapeutic laryngeal band, a therapeutic face band and / or a therapeutic belly band.

In addition, a therapeutic seat pad has been proposed for stimulating the patient's neurons to suppress pathological synchronization activity, allowing the patient to sit on this therapeutic seat pad. As mentioned above, the therapeutic seat pad may constitute or include a therapeutic device. Therefore, the technical features described with respect to the therapeutic device may also be relevant and applicable to this therapeutic seat pad.

In addition, therapeutic soles (ie, insoles) are provided to stimulate the patient's neurons to suppress pathological synchronous activity. As mentioned above, the therapeutic sole may constitute or include a therapeutic device. Therefore, the technical features described with respect to the therapeutic device may also be relevant and applicable to this therapeutic sole.

In addition, therapeutic systems for stimulating the patient's neurons to suppress pathological synchronous activity may be proposed, the therapeutic system comprising two or more of the aforementioned therapeutic devices. Specifically, the treatment system may further include a central control device for generating control signals for the treatment device. For example, the central control device can be configured by the control unit of one of the treatment devices.

Furthermore, therapeutic methods for stimulating the patient's neurons to suppress pathological synchronization activity are proposed. The method may include providing at least three non-invasive stimulus units for generating stimuli to the patient's body and selectively and intermittently activating the stimulus units according to a sequence of periods of activity. Thus, the number n of stimulus units activated simultaneously during each active period can vary widely throughout the sequence, and three stimulating units can be activated simultaneously during at least one active period of the active period. Alternatively or additionally, a single stimulus unit may be activated exclusively or individually during at least one period of activity. Alternatively or additionally, two stimulus units may be activated exclusively at the same time during at least one active period. The proposed method can be used for therapeutic devices as described above. Therefore, the technical features described with respect to the therapeutic device may also be relevant and applicable to this method.

10 Treatment device 12 Stimulation unit 14 Control unit 16 Connection line 18 Sensor unit 20 Connection line 22 Treatment glove 24 Sensor unit 25 Patient head 26 Patient hand 28 Communication unit 30 Still another communication unit 34 EEG electrode 36 Controller 38 Treatment Neck and / or shoulder band 40 Therapeutic laryngeal band 42 Therapeutic face mask or band 44 Therapeutic seat pad 46 Therapeutic abdominal wrap

Claims (26)

A therapeutic device for stimulating a patient's neurons to suppress pathological synchronization activity.
With at least three non-invasive stimulus units to generate stimuli to the patient's body,
It is equipped with a control unit for selectively and intermittently operating the stimulation unit within a sequence of active periods.
A therapeutic device in which the control unit is configured to variously determine the number n of the stimulation units that are simultaneously activated during each of the active periods, for each of the active periods, throughout the sequence of the active periods. The therapeutic device of claim 1, wherein the control unit is configured to determine at least three simultaneously activated stimulation units during at least one of the active periods of the sequence. The therapeutic apparatus according to claim 1 or 2, wherein the stimulation unit is configured to generate stimulation to various parts of the patient's body. The therapeutic device according to any one of claims 1 to 3, wherein the stimulation unit is configured to generate a stimulus on the body surface of the patient. The therapeutic apparatus according to any one of claims 1 to 4, wherein the stimulation unit is configured to generate tactile stimulus and / or vibration stimulus and / or electrical stimulus. The treatment device according to any one of claims 1 to 5, wherein n is an integer between 1 and the total number of stimulation units included in the treatment device. The therapeutic device according to any one of claims 1 to 6, wherein the number n is an integer between 1 and u-1, when the device comprises a number u of more than three. The control unit stochastically and / or deterministically and / or a combination of probability theory and determinism the number n of the stimulus units that are simultaneously activated during the activity period. The treatment apparatus according to any one of claims 1 to 7, which is configured to determine. 1. The control unit is configured to variously select the determined number n of various stimulation units from the at least three stimulation units of the device throughout the sequence of the active period. 8. The treatment device according to any one of 8. The control unit is to select a single first stimulus unit that is individually actuated during the first activity period and a single second stimulus unit that is individually actuated during the second activity period. The therapeutic device according to any one of claims 1 to 9, which is configured. The treatment device of claim 10, wherein the control unit is configured to select at least two stimulus units that are simultaneously activated during a third period of activity. For each period of activity, the control unit determines the determined number n of stimulus units from the at least three stimulus units of the treatment device as stochastic and / or deterministic and / or probabilistic. The treatment apparatus according to any one of claims 1 to 11, configured to be selected by a combination of theories. The control unit simultaneously activates the stimulus unit in each of the active periods into a single stimulus unit in the sequence and / or in the active period in the sequence. The treatment apparatus according to any one of claims 1 to 12, which is configured to be selected according to a predetermined probability or a predetermined frequency of occurrence of the combination of. The predetermined frequency of occurrence is set to prevent the single stimulus unit from being activated individually within the sequence and / or a particular combination of the stimulus units being activated simultaneously within the sequence. Item 13. The treatment device according to item 13. One of claims 1 to 14, wherein the control unit is configured to variously select one operation mode from a predetermined set of operation modes of each of the selected stimulation units for each of the selected stimulation units. The treatment device described in. The treatment according to claim 16, wherein the motion mode of each of the stimulus units differs in the characteristics of the stimulus generated by the stimulus unit in terms of stimulus duration, stimulus intensity, stimulus frequency and / or stimulus time change. Device. The treatment apparatus according to any one of claims 1 to 15, wherein the control unit is configured to define a rest period between consecutive periods of activity. The treatment apparatus according to claim 18, wherein the control unit is configured to variously determine the duration of each rest period throughout the sequence. 19. The therapeutic apparatus according to claim 19, wherein the control unit is configured to determine the duration of each of the rest periods stochastically and / or deterministically, and / or a combination of probability theory and determinism. .. A sensor unit for measuring the stimulating action on the neuron is further provided, and the control unit adapts the stimulus generated by the stimulating unit and / or the sequence of the active period according to the information measured by the sensor unit. The treatment apparatus according to any one of claims 1 to 20, which is configured as described above. A therapeutic glove that is fixed in the patient's hand and stimulates the patient's neurons to suppress pathological synchronization activity.
With at least three non-invasive stimulus units to generate stimuli to the patient's body,
It is equipped with a control unit for selectively and intermittently operating the stimulation unit within a sequence of active periods.
A therapeutic glove in which the control unit is configured to varyly determine the number n of the stimulation units that are simultaneously activated during each of the active periods, for each of the active periods, throughout the sequence of the active periods. A therapeutic band that is fixed to the patient's body and stimulates the patient's neurons to suppress pathological synchronization activity.
With at least three non-invasive stimulus units to generate stimuli to the patient's body,
It is equipped with a control unit for selectively and intermittently operating the stimulation unit within a sequence of active periods.
A therapeutic band in which the control units are configured to varyly determine the number n of the stimulation units that are simultaneously activated during each of the active periods, for each of the active periods, throughout the sequence of the active periods. A therapeutic seat pad for stimulating a patient's neurons to suppress pathological synchronization activity.
With at least three non-invasive stimulus units to generate stimuli to the patient's body,
It is equipped with a control unit for selectively and intermittently operating the stimulation unit within a sequence of active periods.
A therapeutic seat pad in which the control unit is configured to variously determine the number n of the stimulation units that are simultaneously activated during each of the active periods, for each of the active periods, throughout the sequence of the active periods. A therapeutic sole that stimulates the patient's neurons to suppress pathological synchronization activity.
With at least three non-invasive stimulus units to generate stimuli to the patient's body,
It is equipped with a control unit for selectively and intermittently operating the stimulation unit within a sequence of active periods.
A therapeutic sole configured such that the control unit variously determines the number n of the stimulation units that are simultaneously activated during each of the active periods over the entire sequence of the active periods. A treatment system for stimulating a patient's neurons to suppress pathological synchronous activity, the treatment system comprising two or more treatment devices according to any one of claims 1-25. It is a therapeutic method for stimulating the patient's neurons to suppress pathological synchronization activity.
A step of providing at least three non-invasive stimulus units for generating stimuli to the patient's body, and
The number n of the stimulus units that are simultaneously activated during each of the active periods, including the step of selectively and intermittently activating the stimulus units according to a sequence of active periods, vary throughout the sequence. A method in which three of the stimulation units are simultaneously activated during at least one active period.

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